Structural insights, spectral and H-bond analyses, of nitrofurantoin-phenazine cocrystal and comparison of its chemical reactivity with other nitrofurantoin cocrystals

This work gives the unified insight of vibrational spectroscopy (FT-IR and FT-Raman) and density functional theory (DFT) calculations to get an understanding of the hydrogen bonding pattern and chemical reactivity of a cocrystal of nitrofurantoin (NF, an antibacterial drug) with phenazine (PHEN). FT-Raman (10 0-3700 cm(-1)) and infrared (400-4000 cm(-1)) spectroscopic techniques were used for the characterization of the NF-PHEN cocrystal and NF drug itself in the solid state. The intermolecular H-bonding is affirmed by natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) studies. The reactivity studies of NF-PHEN through global and local reactivity descriptors have also been performed. The global reactivity parameters of NF-PHEN have been compared with that of NF itself and two other cocrystals of NF [nitrofurantoin-melamine monohydrate (NF-MELA-H2O) and nitrofurantoinurea (NF-urea)] where hetero-atom (nitrogen) rich coformers have been used. It is established that all the three cocrystals show more chemical reactivity than NF itself. And amongst three NF cocrystals, NF-MELAH(2)O is most stable while NF-PHEN is chemically most reactive. In other words, NF-PHEN is chemically softer than other two cocrystals. Molecular electrostatic potential (MEP) map has also been studied as it is correlated to the electronic density and is advantageous in considering sites for electrophilic and nucleophilic strikes together with hydrogen bonding interactions. Molar refractivity (MR) value of NF-PHEN falls within the range set by Lipinski's modified rule and suggests that the studied cocrystal may show drug likeness. Accordingly, structural and reactivity studies could be successfully employed to a pharmaceutical cocrystal, NF-PHEN, considered in this study and for various other multicomponent crystals in gaining insights into their hydrogen bond interactions and physicochemical properties. (C) 2021 Published by Elsevier B.V.

Automated summary

This study provides unified insight into the vibrational spectroscopy and density functional theory calculations of a cocrystal of nitrofurantoin with phenazine, revealing the hydrogen bonding pattern and chemical reactivity. The cocrystal shows higher chemical reactivity compared to nitrofurantoin alone, with NF-PHEN being the most chemically reactive among three cocrystals.